sitagliptin-phosphate and Weight-Loss

Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes.. We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction.. In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD  -0.99; 95% CI; (-1.87, -0.12); p=0.026)) and sitagliptin+metformin treated groups (MD  -1.09; 95% CI; (-1.69, -0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD  -0.23; 95% CI; (-0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD -0.52; 95% CI; (-0.96, 0.08); p=0.020)) comparing to placebo.. Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Obesity; Overweight; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Weight Loss

To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies.. We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous.. Seven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.. Sitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2 kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin.. CRD42016033983.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Outcome Assessment, Health Care; Sitagliptin Phosphate; Sulfonylurea Compounds; Weight Loss; Young Adult

This Practice Pearl provides a review and brief commentary of the 24-week, double-blind, parallel-group, randomized, Phase III study by Roden et al., which assessed the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin, 10 mg or 25 mg as monotherapy, versus placebo and the dipeptidyl peptidase-4 inhibitor sitagliptin, in previously untreated patients with type 2 diabetes mellitus (T2DM). Compared to placebo, empagliflozin improved glycemic control, with additional benefits on bodyweight and systolic blood pressure, versus placebo and sitagliptin. Treatment was well tolerated. The authors concluded that empagliflozin is a potential new approach to treat patients with T2DM who are inadequately controlled with diet and exercise alone. This paper advances our understanding of empagliflozin, which so far, appears to be a promising therapeutic option for the management of patients with T2DM.

Topics: Adult; Benzhydryl Compounds; Blood Pressure; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.. Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models.. A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I(2)  = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001).. The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.

Topics: Adamantane; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Islam; Liraglutide; Nitriles; Observational Studies as Topic; Pioglitazone; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Vildagliptin; Weight Loss

Effective, evidence-based management of type 2 diabetes (T2D) requires the integration of the best available evidence with clinical experience and patient preferences.. Studies published from 2000 to 2012 evaluating glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were identified using PubMed. The author contextualized the study findings with his clinical experience.. Incretin-based therapy targets multiple dysfunctional organs in T2D. Injectable GLP-1RAs provide substantial glycemic control and weight reduction; while oral DPP-4 inhibitors provide moderate glycemic control and weight neutrality. Both classes are effective, well tolerated, and associated with a low incidence of hypoglycemia when used alone or in combination with other antidiabetes agents. GLP-1RAs are associated with transient nausea and, like DPP-4 inhibitors, rare pancreatitis.. Data indicate and clinical experience confirms that incretins are well tolerated in appropriate patients and provide sustained glycemic control and weight loss or weight neutrality throughout T2D progression.

Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Linagliptin; Liraglutide; Peptides; Piperidines; Purines; Pyrazines; Quinazolines; Receptors, Glucagon; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Uracil; Venoms; Weight Loss

Incretin-based therapies have a glucose-dependent mode of action that results in excellent glucose-lowering efficacy with very low risk of hypoglycaemia, and weight neutrality [dipeptidyl peptidase-4 (DPP-4) inhibitors] or weight loss [glucagon-like peptide-1 (GLP-1) receptor agonists], in people with type 2 diabetes mellitus (T2DM). Patient-reported outcomes (PROs) complement physician evaluations of efficacy and tolerability and offer insights into the subjective experience of using modern diabetes treatments. We conducted a systematic search of clinical trials of the GLP-1 receptor agonists liraglutide, exenatide and long-acting exenatide, one of which included the oral DPP-4 inhibitor sitagliptin as a comparator. No other PRO data for DPP-4 inhibitors were identified. This review summarizes PRO data from eight clinical trials, the majority of which used the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and/or Impact of Weight on Quality of Life-Lite (IWQOL-Lite) to evaluate patient experience. People with T2DM were highly satisfied with modern incretin-based therapies compared with traditional therapies. Treatment satisfaction (including perceptions of convenience and flexibility) was high and generally higher with GLP-1 agonists in association with their greater glucose-lowering efficacy and tendency to facilitate weight loss. Weight-related quality of life (QoL) also improved in people using incretin therapies. The glycaemic improvements achieved with GLP-1 receptor agonists, coupled with the low incidence of hypoglycaemia and ability to cause weight loss, seemed to offset potential concern about injections. It is plausible that superior patient-reported benefits found in clinical trials may translate into improved, clinically meaningful, long-term outcomes through increased treatment acceptability. Long-term, prospective data are needed to ascertain whether this is the case in practice.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Exenatide; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Incretins; Injections, Subcutaneous; Liraglutide; Male; Medication Adherence; Patient Satisfaction; Peptides; Pyrazines; Self Care; Sitagliptin Phosphate; Surveys and Questionnaires; Treatment Outcome; Triazoles; Venoms; Weight Loss

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Drug Approval; Drug Therapy, Combination; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Insulin; Male; Metformin; Middle Aged; Pyrazines; Risk Factors; Satiety Response; Sitagliptin Phosphate; Triazoles; Weight Loss

A systematic review of the literature, in combination with a meta-analysis of randomized controlled trials comparing treatments with placebo, was conducted to provide an update on the clinical efficacy and safety of incretin-based medications in adult patients with type 2 diabetes.. A literature search (2000-2009) identified 38 placebo-controlled trials (phase II or later - parallel design) comparing exenatide (n = 8), liraglutide (n = 7), vildagliptin (n = 11) and sitagliptin (n = 12) with placebo. Outcomes were change from baseline in HbA(1c) and in weight, and the number of patient-reported hypoglycemic episodes. HbA(1c) and weight outcomes were analyzed as weighted mean differences (WMD), and the number of hypoglycemic episodes as relative risks (RR).. Patients receiving liraglutide showed greater reduction in HbA(1c) in comparison to placebo (WMD = -1.03, 95% confidence interval, CI = -1.16 to -0.90, p < 0.001) than those on sitagliptin (WMD = -0.79, 95% CI = -0.93 to -0.65, p < 0.001), exenatide (WMD = -0.75, 95% CI = -0.83 to -0.67, p < 0.001) or vildagliptin (WMD = -0.67, 95% CI = -0.83 to -0.52, p < 0.001). Weight was statistically significantly negatively associated with exenatide (WMD = -1.10, 95% CI = -1.32 to -0.87, p < 0.001) and positively associated with sitagliptin (WMD = 0.60, 95% CI = 0.33-0.87, p < 0.001) and vildagliptin (WMD = 0.56, 95% CI = 0.27-0.84, p < 0.001). The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23-5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30-4.11, p = 0.002).. Incretin-based therapies are effective in glycemic control and also offer other advantages such as weight loss (exenatide and liraglutide). This may have an important impact on patient adherence to medication.

Topics: Adamantane; Adult; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Nitriles; Peptides; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin; Weight Loss

To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.. Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR).. Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1).. Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.

Topics: Diet, Reducing; Fibrinolysis; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Inflammation; Insulin Resistance; Liraglutide; Obesity; Plasminogen Activator Inhibitor 1; Prediabetic State; Sitagliptin Phosphate; Weight Loss

To compare the effects of baseline background characteristics in patients treated with dapagliflozin and sitagliptin in the DIVERSITY-CVR study and to analyse the time in range (TIR), a metric for glycaemic control.. This prospective, randomized, multicentre study included 340 Japanese patients with early-stage type 2 diabetes. To examine the effects of dapagliflozin and sitagliptin on glycaemic variability, we re-examined the primary endpoint (glycated haemoglobin [HbA1c] < 7.0%, body weight loss ≥ 3.0%, and avoidance of hypoglycaemia) achievement rate in participants stratified by baseline background characteristics.. Sitagliptin was significantly superior in achieving HbA1c level <7.0% in the lower body mass index (BMI) group (71.1% vs. 43.6%; P < 0.05), with no significant differences in other subgroups. In the lower BMI group, the rate of achievement of TIR > 70% after 24-week treatment was significantly higher with sitagliptin than with dapagliflozin (91.9% vs. 69.4%; P < 0.05). In contrast, dapagliflozin was superior to sitagliptin in achieving TIR > 70% in the higher BMI group (85.7% vs. 52.9%; P < 0.01).. In Japanese patients with early-stage type 2 diabetes, sitagliptin was associated with improved TIR in patients with a lower BMI. Dapagliflozin was effective in patients with a higher BMI.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; East Asian People; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome; Weight Loss

To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment.. A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test.. Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR).. Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors.

Topics: Adult; Appetite; Body Fat Distribution; Body Weight; Caloric Restriction; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Eating; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Liraglutide; Obesity; Prediabetic State; Sitagliptin Phosphate; Weight Loss

Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight.. This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring.. Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes. Trial registration Trial number, UMIN000028014; registered on June 30, 2017.

Topics: Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucosides; Glycated Hemoglobin; Humans; Japan; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Risk Assessment; Risk Factors; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).. In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.. Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001).. In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

Topics: Administration, Oral; Constipation; Diabetes Mellitus, Type 2; Diarrhea; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Incretins; Injections, Subcutaneous; Japan; Nausea; Patient Dropouts; Severity of Illness Index; Sitagliptin Phosphate; Weight Loss

To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established.. Subjects with inadequately controlled type 2 diabetes (drug-naïve or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects.. Clinically relevant weight-loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects).. In SUSTAIN 1 to 5, semaglutide-induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Nausea; Sitagliptin Phosphate; Treatment Outcome; Vomiting; Weight Loss

The aim of this study was to evaluate the efficacy and safety of sitagliptin administered to elderly patients with type 2 diabetes mellitus (T2DM) for 1 year as compared with glimepiride. Patients aged ≥60 years with T2DM and inadequately controlled blood glucose were randomly assigned to sitagliptin 50 mg once daily or glimepiride 0.5 mg once daily for 52 weeks. The primary efficacy endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 52. Secondary efficacy endpoints included self-monitored blood glucose and weight. Safety endpoints were adverse events including hypoglycaemia. Administration of sitagliptin or glimepiride to elderly patients with T2DM resulted in a significant decrease in HbA1c change from baseline. At 52 weeks, the least squares mean difference between the treatments was 0.11% (95% confidence interval [CI] -0.02 to 0.24; P = .087) (1.2 mmol/mol [-0.2 to 2.6]). The upper limit of the CI was below the predefined non-inferiority margin (0.3% [3.3 mmol/mol]), demonstrating non-inferiority of sitagliptin to glimepiride for the primary endpoint. Sitagliptin resulted in a significantly lower incidence rate of non-serious hypoglycaemia than glimepiride during the 52 weeks (4.7% vs 16.1%; P = .002); thus, sitagliptin is a useful therapeutic option for elderly patients with T2DM.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Equivalence Trials as Topic; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Japan; Middle Aged; Reproducibility of Results; Severity of Illness Index; Sitagliptin Phosphate; Sulfonylurea Compounds; Weight Loss

To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks.. Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports.. Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated.. A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks.. www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Racial Groups; Sitagliptin Phosphate; Sulfonylurea Compounds; Weight Loss; Young Adult

Obesity, dyslipidemia and hypertension are major risk factors for cardiovascular disease and its associated complications. To evaluate the beneficial effects of sitagliptin and metformin in non-diabetic dyslipidemic and hypertensive patients. A prospective randomized clinical trial was conducted on 70 newly diagnosed dyslipidemic patients with BMI > 25 and blood pressure > 130/80 at outpatient clinic of medical unit-1 of Sheikh Medical College/Hospital, Rahim Yar Khan. They were divided in to three groups each containing 35 patients; First group served as a healthy control while second and third study groups were given tablet sitagliptin 50mg and tab metformin 850mg respectively twice a day for twelve weeks. After three months treatment with sitagliptin and metformin there was significant reduction in body weight (Sitagliptin 6.5% vs Metformin 7.65%) and BMI (Sitagliptin 2.2% vs Metformin 2.8%) with p <0.05. Metformin caused a significant reduction in blood pressure with p < 0.05 (i.e. SBP 9.9% & DBP 6.4%) while sitagliptin caused a highly significant p <0.01 reduction in blood pressure (i.e. SBP 15.8% & DBP 12.2%). There was significant improvement in lipid profile with sitagliptin p<0.05. The percent reduction in value of TC, TG and LDL-C was 20.2%, 13.8% and 23.7% while HDL-C value was increased 11.2% respectively. There was highly significant improvement in lipid profile with metformin p<0.01. The percent reduction in value of TC, TG and LDL-C was 27.8%, 28.2% and 40.4% while HDL-C value was increased 16.8% respectively. Both drugs improve cardiometabolic risk factors independently in non-diabetic patients.

Topics: Adult; Antihypertensive Agents; Biomarkers; Blood Pressure; Dipeptidyl-Peptidase IV Inhibitors; Dyslipidemias; Female; Humans; Hypertension; Hypolipidemic Agents; Lipids; Male; Metformin; Middle Aged; Pakistan; Prospective Studies; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Weight Loss

To compare the once-weekly glucagon-like peptide-1 (GLP-1) receptor dulaglutide with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin after 104 weeks of treatment.. This AWARD-5 study was a multicentre, double-blind trial that randomized participants to dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for dulaglutide and sitagliptin at the final endpoint.. Changes in HbA1c at 104 weeks were (least squares mean ± standard error) -0.99 ± 0.06% (-10.82 ± 0.66 mmol/mol), -0.71 ± 0.07% (-7.76 ± 0.77 mmol/mol) and -0.32 ± 0.06% (-3.50 ± 0.66 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg and sitagliptin, respectively (p < 0.001, both dulaglutide doses vs sitagliptin). Weight loss was greater with dulaglutide 1.5 mg (p < 0.001) and similar with 0.75 mg versus sitagliptin (2.88 ± 0.25, 2.39 ± 0.26 and 1.75 ± 0.25 kg, respectively). Gastrointestinal adverse events were more common with dulaglutide 1.5 and 0.75 mg versus sitagliptin (nausea 17 and 15% vs 7%, diarrhoea 16 and 12% vs 6%, vomiting 14 and 8% vs 4% respectively). Pancreatic, thyroid, cardiovascular and hypersensitivity safety were similar across groups.. Dulaglutide doses provided superior glycaemic control and dulaglutide 1.5 mg resulted in greater weight reduction versus sitagliptin at 104 weeks, with acceptable safety.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Male; Metformin; Middle Aged; Recombinant Fusion Proteins; Sitagliptin Phosphate; Treatment Outcome; Weight Loss

To investigate the long-term efficacy and safety of empagliflozin monotherapy compared with placebo and sitagliptin in drug-naïve patients with type 2 diabetes mellitus.. Of 899 patients randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, placebo, or sitagliptin 100 mg once daily for 24 weeks, 615 continued in a double-blind extension trial for ≥52 weeks. Exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76.. Compared with placebo, adjusted mean changes from baseline in HbA1c at week 76 were -0.78 % (95 % CI -0.94, -0.63; p < 0.001) and -0.89 % (95 % CI -1.04, -0.73; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight at week 76 were -1.8 kg (95 % CI -2.4, -1.3; p < 0.001) and -2.0 kg (95 % CI -2.6, -1.5; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to reductions in systolic blood pressure (SBP) compared with placebo in the primary analysis but not in sensitivity analyses. Compared with sitagliptin, empagliflozin 25 mg reduced HbA1c and both empagliflozin doses reduced weight and SBP. Adverse events (AEs) were reported in 76.8, 78.0, 76.4 and 72.2 % of patients on empagliflozin 10 mg, empagliflozin 25 mg, placebo and sitagliptin, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group.. Empagliflozin monotherapy for ≥76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo.. clinicaltrials.gov NCT01289990.

Topics: Adult; Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Weight Loss

Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for treatment of type 2 diabetes mellitus (T2DM). The long-term efficacy and safety of canagliflozin monotherapy were evaluated over 52 weeks in patients with T2DM inadequately controlled with diet and exercise.. This randomized, double-blind, Phase 3 study included a placebo-controlled, 26-week core period (canagliflozin 100 or 300 mg vs placebo) and an active-controlled, 26-week extension (blinded switch of placebo-treated patients to sitagliptin 100 mg [placebo/sitagliptin]).. ClinicalTrials.gov, NCT01081834.. Efficacy endpoints assessed at 52 weeks included changes in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and systolic blood pressure (BP); and percentage changes in body weight and fasting plasma lipids. Adverse events (AEs) were recorded throughout the study. Efficacy data are reported for canagliflozin 100 and 300 mg (placebo/sitagliptin group was used to maintain the double-blind and to serve as a control group for safety purposes; not as an efficacy comparator); safety data are reported for canagliflozin 100 and 300 mg and placebo/sitagliptin.. Efficacy analyses included 451 patients who were randomized and dosed, entered the extension, and did not receive rescue therapy during the core period. Safety analyses included 584 patients who were randomized and dosed. At Week 52, canagliflozin 100 and 300 mg provided dose-related decreases from baseline in HbA1c of -0.81% and -1.11%. Canagliflozin 100 and 300 mg decreased FPG (-1.5 and -2.2 mmol/L [-27.4 and -39.1 mg/dL]), body weight (-3.3% and -4.4%), and systolic BP (-1.4 and -3.9 mmHg); decreased triglycerides and increased HDL-C and LDL-C were also seen. Over 52 weeks, overall AE rates were 67.2%, 66.0%, and 64.1% with canagliflozin 100 and 300 mg and placebo/sitagliptin; rates of serious AEs and AE-related discontinuations were low across groups. Compared with placebo/sitagliptin, canagliflozin was associated with higher rates of genital mycotic infections and AEs related to osmotic diuresis; these led to few discontinuations. Rates of volume depletion AEs and documented hypoglycemia were low across groups.. Canagliflozin monotherapy provided sustained improvement in glycemic control and body weight reduction, and was generally well tolerated in patients with T2DM over 52 weeks.

Topics: Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diet; Double-Blind Method; Exercise; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Placebos; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Treatment Outcome; Triazoles; Triglycerides; Weight Loss

To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.. In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day).. Baseline HbA1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA1c levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA1c levels in patients with baseline values ≥8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%).. These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.

Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Urinary Tract Infections; Weight Loss

The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone.. In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin.. Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (-0.89%, -1.03% and -0.26%; p < 0.001); reductions with canagliflozin 100 and 300 mg were maintained at week 52 (-0.92% and -1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (-2.5 and -3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin.. Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks.

Topics: Blood Glucose; Blood Pressure; Canagliflozin; Candidiasis; Diabetes Mellitus, Type 2; Diuretics, Osmotic; Double-Blind Method; Drug Therapy, Combination; Female; Genital Diseases, Female; Genital Diseases, Male; Glucosides; Humans; Hypoglycemic Agents; Lipids; Male; Metformin; Middle Aged; Pioglitazone; Pyrazines; Sitagliptin Phosphate; Thiazolidinediones; Thiophenes; Treatment Outcome; Triazoles; Weight Loss

Type 2 diabetes mellitus (T2DM) is primarily a self-managed disease in which self-care behaviors play an important role in achieving optimal outcomes. Because self-care does not result in immediate tangible or noticeable benefits, adherence to such a regimen can be confusing, difficult, and frustrating. People are more likely to adhere to treatment regimens that offer benefits from the patient perspective, such as convenience, avoidance of hypoglycemic episodes, and weight loss, compared with regimens that do not. In this study, we explored the impact of the average weight loss amount demonstrated with canagliflozin treatment on improvement in 3 patient-relevant outcomes that have been linked to performance of healthy behaviors and better outcomes in T2DM: weight-related quality of life, as measured by the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, and satisfaction with physical health and emotional health, as measured by the Current Health Satisfaction Questionnaire (CHES-Q), using data from a previously reported study. Weight loss of an amount demonstrated in clinical trials of canagliflozin was associated with improvements in weight-related quality of life and satisfaction with physical and emotional health, concepts shown to be important to the persistent and consistent performance of healthy behaviors.

Topics: Adult; Age Factors; Aged; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Health Behavior; Humans; Hypoglycemic Agents; Male; Middle Aged; Personal Satisfaction; Pyrazines; Quality of Life; Self Efficacy; Sex Factors; Sexual Behavior; Sitagliptin Phosphate; Thiophenes; Triazoles; Weight Loss

The aim of this study was to evaluate the effectiveness of sitagliptin, alone or in combination with metformin, in kidney transplant patients with newly diagnosed new-onset diabetes mellitus after transplant who had inadequate glycemic control, compared with a group of patients receiving insulin glargine with special emphasis on weight gain.. Newly diagnosed renal transplant patients with new-onset diabetes mellitus after a transplant was defined by a blood glucose ≥ 11.1 mmol/L after an oral glucose tolerance test were examined. They were treated with standard immunosuppression composed of triple therapy with tacrolimus or cyclosporine, mycophenolate mofetil or azathioprine, and prednisone. They had stable graft function for more than 6 months after the transplant.. Patients with new-onset diabetes mellitus after transplant (n=28) whose glycemia was not controlled adequately with oral hypoglycemic agents (either alone or in combination) received oral sitagliptin 100 mg once daily in addition to existing therapy for 12 weeks. Patients who received insulin glargine as add-on therapy (n=17) served as the control group. Data analyses included glycated hemoglobin, fasting plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia. We found significant reductions in glycated hemoglobin and fasting plasma glucose values after 12 weeks of additional sitagliptin therapy that were comparable to those with insulin glargine. While the addition of stagliptin resulted in a small weight loss (0.4 kg), the addition of insulin glargine resulted in a weight gain (0.8 kg). The overall incidence of adverse experiences was low and generally mild in both groups.. In a group of renal transplant recipients with new-onset diabetes mellitus after a transplant in whom glycemia was not controlled adequately by oral hypoglycemic agents, the addition of sitagliptin helped to achieve glycemic control similar to insulin glargine but with a marginal weight advantage.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Kidney Transplantation; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Gain; Weight Loss

We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus (T2DM) treated with liraglutide versus comparator diabetes therapies.. Twenty-six-week data from seven phase 3, randomized trials in the liraglutide T2DM development programme were analysed by trial and treatment group: liraglutide (1.2 and 1.8 mg), active comparator and placebo. Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline; impact of body mass index (BMI) and gastrointestinal (GI) adverse events (AEs) on weight change and correlation of weight change with change in glycosylated haemoglobin (HbA1c).. A number of subjects experienced >5% weight loss during the trials (24.4% liraglutide 1.8 mg and 17.7% liraglutide 1.2 mg; 17.7% exenatide, 10.0% sitagliptin, 3.6-7.0% sulphonylurea, 2.6% thiazolidinedione and 2.6% glargine; 9.9% placebo). More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide. Across trials, higher initial BMI was associated with slightly greater weight loss with liraglutide. Mean weight loss increased slightly the longer GI AEs persisted. Although HbA1c reduction was slightly larger in higher weight loss categories across treatments (including placebo), sample sizes were small and no clear correlation could be determined. Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced; thus, not all HbA1c-lowering effect appears weight mediated.. The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis. Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Middle Aged; Peptides; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Triazoles; Venoms; Weight Loss

The aim of this trial was to evaluate the efficacy and safety of the combination of once-daily insulin detemir (IDet) and sitagliptin (SITA) versus SITA ± sulphonylurea (SU), both in combination with metformin (MET) in insulin-naive subjects.. In a 26-week, open-label, randomized, parallel-group study in type 2 diabetes, insulin-naive subjects concomitantly treated with MET ± second oral antidiabetic drug (OAD) were randomized 1 : 1 to IDet + SITA + MET or SITA + MET ± SU. All continued with MET treatment, and those treated with SU continued if randomized to SITA + MET ± SU. Efficacy endpoints included glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), 9-point self-measured plasma glucose (SMPG), weight, body mass index (BMI). Safety endpoints included adverse events (AEs) and hypoglycaemia.. Significantly higher reductions in HbA1c, FPG and SMPG were achieved with IDet + SITA + MET compared with SITA + MET ± SU. Estimated HbA1c decreased by 1.44% in the IDet + SITA + MET group versus 0.89% in SITA + MET ± SU, p < 0.001. FPG decreased by 3.7 mmol/l (66.3 mg/dl) versus 1.2 mmol/l (22.2 mg/dl), p < 0.001, respectively. Small decreases in weight and BMI were observed in both arms, with no significant differences. AEs were mild or moderate and were more common in the SITA + MET ± SU arm than in the IDet + SITA + MET arm. There was no major hypoglycaemia. Observed rates of hypoglycaemia were very low (1.3/1.7 episodes/patient year) in both arms. The subgroup treated with MET and SUs prior to the trial achieved similar results.. The combination of once-daily IDet with SITA showed a clinically and significantly better improvement in glycaemic control than SITA in combination with or without SUs. Both regimens were associated with a low rate of hypoglycaemia and slight weight reduction.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes.. In an open-label, parallel-group trial, metformin-treated participants were randomised to liraglutide 1.2 mg/day (n=225), liraglutide 1.8 mg/day (n=221) or sitagliptin 100 mg/day (n=219) for 26 weeks (main phase). Participants continued the same treatment in a 26-week extension.. Liraglutide (1.2 or 1.8 mg) was superior to sitagliptin for reducing HbA(1c) from baseline (8.4-8.5%) to 52 weeks: -1.29% and -1.51% vs. -0.88% respectively. Estimated mean treatment differences between liraglutide and sitagliptin were as follows: -0.40% (95% confidence interval -0.59 to -0.22) for 1.2 mg and -0.63% (-0.81 to -0.44) for 1.8 mg (both p<0.0001). Weight loss was greater with liraglutide 1.2 mg (-2.78 kg) and 1.8 mg (-3.68 kg) than sitagliptin (-1.16 kg) (both p<0.0001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin (p=0.03). Proportions of participants reporting adverse events were generally comparable; minor hypoglycaemia was 8.1%, 8.3% and 6.4% for liraglutide 1.2 mg, 1.8 mg and sitagliptin respectively. Gastrointestinal side effects, mainly nausea, initially occurred more frequently with liraglutide, but declined after several weeks..   Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks. Treatment satisfaction was significantly greater with 1.8 mg liraglutide, similar to 26-week results. The safety profiles of liraglutide and sitagliptin are consistent with previous reports.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US.. Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target.. Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively.. Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US.. Novo Nordisk A/S.

Topics: Benzhydryl Compounds; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Middle Aged; Sitagliptin Phosphate; United States; Weight Loss

The aims of this study were to assess glycemic control, weight loss, and durability of glycemic control in patients initiated on canagliflozin (CANA) versus sitagliptin (SITA).. Adults with type II diabetes mellitus initiated on CANA or SITA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records - US database (03/29/2012-04/30/2016). Inverse probability of treatment weighting accounted for baseline differences between cohorts. Outcomes were compared using weighted Cox regression and Kaplan-Meier curves and included time to reaching HbA1c thresholds (<7%[53 mmol/mol], <8%[64 mmol/mol], <9%[75 mmol/mol]), weight loss ≥5%, failure to maintain HbA1c below threshold, new antihyperglycemic (AHA) prescription, and failure to maintain HbA1c/new AHA prescription.. Weighted cohorts were well balanced (N. CANA patients were more likely to reach HbA1c and weight loss thresholds and maintain HbA1c below threshold versus SITA patients, while being less likely to have a prescription for a new AHA, suggesting more durable glycemic control with CANA.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Canagliflozin; Cohort Studies; Comparative Effectiveness Research; Databases, Factual; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Retrospective Studies; Sitagliptin Phosphate; Time Factors; United States; Weight Loss; Young Adult

The recent LIRA-SWITCH trial showed that switching from sitagliptin 100 mg to liraglutide 1.8 mg led to statistically significant and clinically relevant improvements in glycated haemoglobin (HbA1C) and body mass index (BMI). Based on these findings, the aim of the present study was to assess the long-term cost-effectiveness of switching from sitagliptin to liraglutide in patients with type 2 diabetes in the UK.. The IQVIA CORE Diabetes Model Version 8.5+ was used to project costs and clinical outcomes over patients' lifetimes. Baseline cohort characteristics and treatment effects were derived from the LIRA-SWITCH trial. Future costs and clinical benefits were discounted at 3.5% annually. Costs were accounted in pounds sterling (GBP) and expressed in 2016 values. One-way and probabilistic sensitivity analyses were performed.. Model projections showed improved quality-adjusted life expectancy for patients with poorly controlled HbA1c upon switching from sitagliptin to liraglutide, compared with continuing sitagliptin treatment (9.18 vs 9.02 quality-adjusted life years [QALYs]). Treatment switching was associated with increased overall costs (GBP 24737 vs GBP 22362). Higher pharmacy costs were partially offset by reduced diabetes-related complication costs in patients who switched to liraglutide. Switching to liraglutide was associated with an incremental cost-effectiveness ratio of GBP 15423 per QALY gained vs continuing with sitagliptin treatment.. Switching from sitagliptin 100 mg to liraglutide 1.8 mg in patients with poor glycaemic control was projected to improve clinical outcomes and is likely to be considered cost-effective in the UK setting and, therefore, a good use of limited NHS resources.

Topics: Anti-Obesity Agents; Body Mass Index; Cohort Studies; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Monitoring; Drug Resistance; Glucagon-Like Peptide-1 Receptor; Health Care Costs; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Models, Economic; Overweight; Quality of Life; Risk Factors; Sitagliptin Phosphate; United Kingdom; Weight Loss

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prognosis; Retrospective Studies; Sitagliptin Phosphate; Treatment Outcome; Weight Loss

Intentional weight loss, primarily by improving insulin resistance, is known to decrease the need for anti-diabetic medications. In this study, we assess the magnitude of weight loss that resulted in dose reductions or discontinuation of anti-diabetic medications in overweight or obese patients with type 2 diabetes (DM) undergoing weight loss treatment.. Case records of 50 overweight or obese patients with DM who successfully decreased dosage or discontinued diabetes medications after losing weight via attendance at two University-based, outpatient weight management centers were analyzed. Follow-up visits, weight reduction interventions, and decisions for dose reductions or discontinuation of medications were individualized to patient needs by the treating physician.. Mean starting BMI was 35 kg/m(2), mean age 53.4 years, and 58% were male. All 50 used at least one anti-diabetic medication (30 metformin, 39 sulfonylureas, 31 insulin, 21 sitagliptin) to manage blood sugar. Mean duration of follow-up was 30.2 months. Mean weight loss was 10.8 ± 4.1 kgs (11.1% of initial body weight ± 4.7%). 22/50 patients (44%) discontinued anti-diabetes medications (14 sulfonylureas [36%], 7 insulin [23%], 4 sitagliptin [19%]). The mean percentage weight loss achieved at the point of successful discontinuation of medication was 11.2% ± 3.5% (14% for sulphonylureas, 11% for insulin, and 7.1% for sitagliptin). Mean percentage weight loss of 5.6% ± 2.8% (5.1% for sulphonylureas, 4.3% for insulin, and 7.1% for sitagliptin) was required for initial dose reduction. For every 5% weight loss, predicted dose reductions were sulphonylureas, 39%; insulin, 42%; and any anti-diabetic medications, 49%.. Among overweight or obese patients with type 2 diabetes, intentional weight loss of 7-14% was typically required for full discontinuation of at least one anti-diabetic medication. Discontinuation of insulin was achieved at a mean weight reduction of 11% of initial body weight.

Topics: Adult; Aged; Body Mass Index; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Obesity; Overweight; Pyrazines; Regression Analysis; Retrospective Studies; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles; Weight Loss

Weight loss in patients with type 2 diabetes can improve glycemic control, lower blood pressure, and improve dyslipidemia. Glucagon-like peptide (GLP-1) receptor agonists are associated with weight loss and have potentially beneficial effects on cardiovascular risk biomarkers; however, there is limited information to indicate whether these effects remain outside of clinical trials.. Medical records from the General Electric Centricity research database were analyzed retrospectively to evaluate the relationship between weight loss and glycemic control and changes in blood pressure and lipids in patients with type 2 diabetes initiating therapy with exenatide, sitagliptin, or insulin. Baseline and follow-up (90-365 days after the index date) for weight, A1C, fasting blood glucose (FBG), blood pressure, triglycerides, and LDL, HDL, and total cholesterol were assessed.. A total of 6,280, 5,861, and 32,398 patients receiving exenatide, sitagliptin, or insulin, respectively, were included in the analysis. Exenatide-treated patients lost a mean +/- SD of 3.0 +/- 7.33 kg, sitagliptin-treated patients lost 1.1 +/- 5.39 kg, and insulin-treated patients gained 0.6 +/- 9.49 kg. There was a significant association between weight loss and a reduction in A1C and FBG with exenatide only and a reduction in blood pressure for all therapies. Weight loss was associated with some improvements in lipids, primarily in the GLP-1 receptor agonist group, with little association in the insulin group.. Weight reduction with GLP-1 receptor agonists was associated with a shift toward a more favorable cardiovascular risk profile. Outcome trials are needed to determine whether improvement in biomarkers translates into a reduction in cardiovascular events in patients with type 2 diabetes.

Topics: Aged; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Multivariate Analysis; Peptides; Pyrazines; Sitagliptin Phosphate; Triazoles; Venoms; Weight Loss

Topics: Adamantane; Blood Pressure; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Insulin-Secreting Cells; Lipids; Liraglutide; Male; Middle Aged; Peptides; Pyrazines; Sitagliptin Phosphate; Triazoles; Venoms; Weight Loss

The overall safety profiles of GLP-1 agonists and DPP-4 inhibitors are favorable, with a low incidence of hypoglycemia. This attribute, along with their weight and cardiovascular benefits, particularly with the GLP-1 agonists, make them appropriate choices in our 3 patient cases. Ongoing safety investigations with GLP-1 agonists and DPP-4 inhibitors will provide further clarity to the complete safety profiles of these agents.

Topics: Adamantane; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Liraglutide; Male; Metformin; Middle Aged; Peptides; Pyrazines; Receptors, Glucagon; Risk; Sitagliptin Phosphate; Triazoles; Venoms; Weight Loss

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Metformin; Peptides; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Venoms; Weight Loss